Phospholipase Cδ1 is a Guanine Nucleotide Exchanging Factor for Transglutaminase II (Gα(h)) and Promotes α(1B)-Adrenoreceptor-mediated GTP Binding and Intracellular Calcium Release

Abstract

Effectors involved in G protein-coupled receptor signaling modulate activity of GTPases through GTPase-activating protein or guanine nucleotide exchanging factor (GEF). Phospholipase C delta1 (PLC delta1) is an effector in tissue transglutaminase (TGII)-mediated alpha (1B)-adreno-receptor (alpha (1B)AR) signaling. We investigated whether PLC delta1 modulates TGII: activity. PLC delta1 stimulated GDP release from TGII in a concentration-dependent manner, resulting in an increase in GTP gammaS binding to TGII. PLC delta1 also inhibited GTP hydrolysis by TGII that was independent from the alpha (1B)AR. These results indicate that PLC delta1 is GEF for TGII and stabilizes the GTP TGII complex. When GEF function of PLC delta1 was compared with that of the alpha (1B)AR, the alpha (1B)AR-mediated GTP gammaS binding to TGII was greater than PLC delta1-mediated binding and was accelerated in the presence of PLC delta1. Thus, the LU,,AR is the prime GEF for TGII, and GEF activity of PLC delta1 promotes coupling efficacy of this signaling system. Overexpression of TGII and its mutants with and without PLC delta1 resulted in an increase in alpha (1B)AR-stimulated Ca2+ release from intracellular stores in a TGII-specific manner. We conclude that PLC delta1 assists the alpha (1B)AR function through its GEF action and is primarily activated by the coupling of TGII to the cognate receptors.